A closed flock of white leghorn chickens maintained at Cornell University for over 35 years, the Cornell "C" strain (CS), was found to have a low incidence of hypothyroidism. Selective breeding of hypothyroid CS birds resulted in a strain named the Obese strain (OS), in which practically all individuals develop hypothyroidism. This disease is characterized by severe lymphocytic infiltration of the thyroid gland and production of thyroglobulin autoantibodies. The neonatal removal of B lymphocytes reduces the severity of disease. Reduction in numbers of T lymphocytes increases the severity of disease. To determine the genetic factors involved in this disease a variety of comparative functional studies have been carried out on the thyroid, thymus and bursa of Fabricius prior to disease development. The thyroids of both CS and OS chickens have one very unusual characteristic - they are partially suppressible by exogenous administration of thyroid hormones. This "autonomous" function is not due to thyroid stimulating immunoglobulins since immunosuppression does not influence this phenomenon. Since the thymus has been shown to play a major role in preventing autoreactivity, a test of thymus function has been carried out on OS and CS chickens. Each was neonatally grafted with skin that differed from the recipient only in respect to minor histocompatibility antigens. If the thymus was surgically removed from both strains at hatching the CS chickens tolerated most of their skin grafts, while the OS rejected most of theirs. This suggests that many cytotoxic cells leave the OS thymus prior to hatching. Related to this point is the finding that the neonatal injection of large amounts of thyroglobulin tolerizes OS chickens and prevents thyroiditis. In conclusion, the OS and CS chickens have abnormal thyroid glands which may predispose them to autoimmune thyroiditis, but the OS chickens develop a much more severe disease due to an abnormal thymus.